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探讨 BPS 暴露对成年雌性小鼠子宫和卵巢的损伤及其机制。

Exploration of the damage and mechanisms of BPS exposure on the uterus and ovary of adult female mice.

机构信息

College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.

College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.

出版信息

Sci Total Environ. 2023 Apr 10;868:161660. doi: 10.1016/j.scitotenv.2023.161660. Epub 2023 Jan 20.

Abstract

Bisphenol S (BPS) has been followed with interest for its endocrine disrupting effects, but exploration on the reproductive system of adult females is lack of deep investigation. In the present study, adult female CD-1 mice were treated with BPS for 28 days at 300 μg/kg/day. After that, uteruses and ovaries were harvested for histopathological examination, RNA-seq analysis, and diseases risk prediction. Hematoxylin-eosin (H&E) staining results showed significant histological alterations in the uterus and ovary of the BPS-exposed mice. Bioinformatics analysis of the RNA-seq screened a certain number of differentially expressed genes (DEGs) in both uterus and ovary between BPS group and their corresponding vehicle control groups (Veh), respectively. Functional enrichment analysis of DEGs found that hormone metabolism and immunoinflammatory related pathways were enriched. Disease risk evaluation of the hub genes was performed and the results indicated that diseases associated with uterus and ovary were mainly related to tumors and cancers. Further pan cancer and ovarian cancer survival analysis based on human diseases database pointed out, Foxa1, Gata3, S100a8 and Shh for uterus, Itgam, Dhcr7, Fdps, Hmgcr, Hsd11b1, Hsd3b1, Ptges, F3, Fn1, Ptger4 and Srd5a1 for ovary were significant correlation with cancer. The findings suggest that BPS causes some histopathological changes, alters the expressions of hub genes, enhances uterine and ovarian tumors or even cancer risks.

摘要

双酚 S(BPS)因其内分泌干扰作用而受到关注,但对成年雌性生殖系统的研究还不够深入。在本研究中,将 CD-1 雌性小鼠用 300μg/kg/天的 BPS 处理 28 天。之后,采集子宫和卵巢进行组织病理学检查、RNA-seq 分析和疾病风险预测。苏木精-伊红(H&E)染色结果显示,BPS 暴露组的小鼠子宫和卵巢组织存在明显的组织学改变。RNA-seq 的生物信息学分析分别筛选出 BPS 组和相应溶剂对照组(Veh)的子宫和卵巢中一定数量的差异表达基因(DEGs)。DEGs 的功能富集分析发现,激素代谢和免疫炎症相关途径被富集。对关键基因进行疾病风险评估的结果表明,与子宫和卵巢相关的疾病主要与肿瘤和癌症有关。进一步基于人类疾病数据库进行泛癌和卵巢癌生存分析,结果表明,与子宫相关的基因有 Foxa1、Gata3、S100a8 和 Shh,与卵巢相关的基因有 Itgam、Dhcr7、Fdps、Hmgcr、Hsd11b1、Hsd3b1、Ptges、F3、Fn1、Ptger4 和 Srd5a1,这些基因与癌症有显著相关性。这些发现表明 BPS 可导致某些组织病理学改变,改变关键基因的表达,增加子宫和卵巢肿瘤甚至癌症的风险。

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